Prophylaxis of Mammary Neoplasia by Selenium Supplementation in the Initiation and Promotion Phases of Chemical Carcinogenesis

Abstract

The present study was designed to determine the chemopreventive effect of dietary selenium supplementation in the initiation or promotion phase of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in rats fed a high-fat diet. Control animals received 0.1 ppm of selenium (as sodium selenite), while experimental groups were supplemented with 5 ppm of selenium for various periods of time: -2 to +24, -2 to +2, +2 to +24, +2 to +12, +12 to +24, and -2 to +12. The time of 7,12-dimethylbenz[a]anthracene administration (50 days of age) was taken as Time 0; minus and plus signs represent the time in weeks before and after 7,12-dimethylbenz[a]anthracene administration, respectively. The following conclusions were drawn from the results: (a) selenium can inhibit both the initiation and promotion phases of carcinogenesis; (b) a continuous intake of selenium is necessary to achieve maximal inhibition of tumorigenesis; (c) the inhibitory effect of selenium in the early promotion phase is probably reversible; and (d) the efficacy of selenium is attenuated when it is given long after carcinogenic injury. In addition, the present investigation also assessed the effectiveness of selenium in inhibiting the reappearance of mammary tumors that had regressed after ovariectomy. By supplementing tumor-bearing animals with 5 ppm of selenium in the diet immediately after endocrine ablation, it was found that tumors reappeared at a slower rate compared to the controls. The data suggested that selenium is not only effective in chemoprevention but can also be used as an adjuvant chemotherapeutic agent.

Footnotes

↵1 This work was supported by Grant CA 27706 from the National Cancer Institute, NIH.